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PubMed1980

Connectin, an elastic protein of muscle. A connectin-like protein from the plasmodium Physarum polycephalum.

A completely sodium dodecyl sulfate-insoluble protein was obtained from plasmodia of Physarum polycephalum. The amino acid composition of this protein was very similar to that of connectin, an elastic protein of muscle. When the protein suspension was treated with 6 M guanidine-HCl in the presence of 0.1 M 2-mercaptoethanol, entanglements of very thin filaments, less than 5 nm in width, were observed under an electron microscope. Since the network structure is almost the same as that of isolated muscle connectin, this plasmodium protein can be regarded as forming an elastic net structure. Using an antiserum against the insoluble protein, it appeared to be located at the peripheral region of the plasmodium. This elastic net structure may act as a cytoskeleton at the cytoplasmic surface of the plasmodium cell membrane.

Amino Acids↗
PubMed2004

Obtaining multiple separate food sources: behavioural intelligence in the Physarum plasmodium.

To evaluate performance in a complex survival task, we studied the morphology of the Physarum plasmodium transportation network when presented with multiple separate food sources. The plasmodium comprises a network of tubular elements through which chemical nutrient, intracellular signals and the viscous body are transported and circulated. When three separate food sources were presented, located at the vertices of a triangle, the tubular network connected them via a short pathway, which was often analogous to the mathematically shortest route known as Steiner's minimum tree (SMT). The other common network shape had high fault tolerance against accidental disconnection of the tubes and was known as cycle (CYC). Pattern selection appeared to be a bistable system involving SMT and CYC. When more than three food sources were presented, the network pattern tended to be a patchwork of SMT and CYC. We therefore concluded that the plasmodium tube network is a well designed and intelligent system.

Animals↗
PubMed1994

A monoclonal antibody that recognizes phosphatidylinositol inhibits induction of tumor necrosis factor alpha by different strains of Plasmodium falciparum.

The clinical symptoms of human malaria are mediated, at least in part, by the release of tumor necrosis factor alpha (TNF) by monocytes and macrophages. We have found that lysates of Plasmodium falciparum-infected erythrocytes stimulate the secretion of TNF from human mononuclear cells, and we have generated several immunoglobulin M monoclonal antibodies (MAbs) that inhibit the induction of TNF by such lysates. Here we describe the properties of MAb 5AB3-11, which causes dose-dependent inhibition of the TNF-inducing factors derived from P. falciparum-infected erythrocytes, with a 50% reduction in TNF secretion at nanomolar concentrations (1 to 2 micrograms/ml). The inhibitory effect appears to be malaria specific in that the induction of TNF by either lipopolysaccharide or lipoteichoic acid is not affected. MAb 5AB3-11 binds to liposomes containing phosphatidylinositol but not to other phospholipid liposomes, showing that it recognizes a phosphatidylinositol-like epitope. MAb 5AB3-11 inhibits the induction of TNF by whole lysates from several strains of P. falciparum which originated from different parts of the tropics, indicating that all of the major TNF-inducing factors derived from Plasmodium-infected erythrocytes contain a common epitope. A phosphatidylinositol-like epitope expressed by Plasmodium-infected erythrocytes may be a suitable immunological target for the prevention or treatment of severe malaria.

Animals↗
PubMed1994

Relationship between intracellular period modulation and external environment change in Physarum plasmodium.

The relationship between intracellular period modulation and external environment change was investigated from the viewpoint of internal information coding in Physarum plasmodium. For the external conditions, concentration changes of attractant (galactose) and repellent (KCl) were used, and the internal responses were measured as the thickness oscillation of the plasmodium. (i) Period of the intracellular oscillation decreased when the concentration of attractant was increased and when the concentration of repellent was decreased. (ii) The period increased when the attractant was decreased and when the repellent was increased. (iii) The larger concentration change induced the larger period modulation. (iv) These responses were observed when the change of concentration was greater than a threshold value. From these results, it was clarified that the relative change in environmental condition is encoded on the relative period modulation in intracellular oscillation. This means that the period change does not directly represent the environment itself but represents the change of its condition. Thus, it is further suggested that the plasmodium estimates the environmental condition based on the relationship between the previous external condition and the present one.

Animals↗
PubMed1997

Secretion of slime, the extracellular matrix of the plasmodium, as visualized with a fluorescent probe and its correlation with locomotion on the substratum.

Slime, the extracellular matrix of Physarum plasmodium, is secreted by the exocytosis of a vesicles that contain a slime precursor. Using an antibody raised against biochemically purified slime, we detected the intracellular localization of the slime vesicle. Slime vesicles are abundant in the advancing front of the plasmodium, as confirmed by electron microscopic observation in two different cross-sectional angles. Screening various reagents, we found that rhodamine-phosphatidylethanolamine (Rh-PE) binds specifically to slime in both its intravesicular and extracellular forms, as confirmed by immunoelectron microscopy using an antibody against fluorochrome rhodamine. The plasmodia vitally stained with Rh-PE exhibited dynamic fluorescent patterns during the course of locomotion. The fluorescence was conspicuous at the periphery of the leading pseudopods and oscillated according to the shuttle streaming that accompanied the relaxation and contraction of the periphery; it was intense in the relaxation phase when pseudopods extended, and became weak in the contraction phase when pseudopods contracted. The results collectively mean that the slime vesicles carried by the cytoplasmic streaming accumulated prior to secretion at the advancing margin of the plasmodium.

Animals↗
PubMed2001

Light irradiation induces fragmentation of the plasmodium, a novel photomorphogenesis in the true slime mold Physarum polycephalum: action spectra and evidence for involvement of the phytochrome.

A new photomorphogenesis was found in the plasmodium of the true slime mold Physarum polycephalum: the plasmodium broke temporarily into equal-sized spherical pieces, each containing about eight nuclei, about 5 h after irradiation with light. Action spectroscopic study showed that UVA, blue and far-red lights were effective, while red light inhibited the far-red-induced fragmentation. Difference absorption spectra of both the living plasmodium and the plasmodial homogenate after alternate irradiation with far-red and red light gave two extremes at 750 and 680 nm, which agreed with those for the induction and inhibition of the fragmentation, respectively. A kinetic model similar to that of phytochrome action explained quantitatively the fluence rate-response curves of the fragmentation. Our results indicate that one of the photoreceptors for the plasmodial fragmentation is a phytochrome.

Animals↗
PubMed2004

Malaria during pregnancy in a reference centre from the Brazilian Amazon: unexpected increase in the frequency of Plasmodium falciparum infections.

Malaria remains globally the most important parasitic disease of man. Data on its deleterious effects during pregnancy have been extensively documented in hyperendemic, holoendemic, and mesoendemic areas from Africa and Asia where Plasmodium falciparum is responsible for almost all infections. However, knowledge about malaria during pregnancy in areas where transmission is unstable and P. vivax is the most prevalent species, such as the Brazilian Amazon, is scarce. Here, we report a preliminary cross sectional descriptive study, carried out at the Fundação de Medicina Tropical do Amazonas, a reference centre for diagnosis and treatment of tropical diseases in the west-Amazon (Manaus, Brazil). A total of 1699 febrile childbearing age women had positive thick blood smears to Plasmodium species, between January and November 1997: 1401 (82.5%) were positive for P. vivax, 286 (16.8%) for P. falciparum and 12 (0.07%) carried mixed infections. From the malarious patients, 195 were pregnant. The ratio of P. falciparum to P. vivax infections in the group of non-pregnant infected women was 1:5.6 while it was 1:2.3 in that of pregnant infected ones. Similar rates or even proportionally more vivax infections during pregnancy were expected to occur, in function of the contraindication of primaquine with the resulting increased P. vivax relapse rates. Such an observation suggests that the mechanism of resistance/susceptibility to infection and/or malaria pathogenesis in pregnant women may differ according to Plasmodium species and that the extensively described increase in the frequencies of malaria infection during pregnancy may be specifically due to P. falciparum infection.

Adolescent↗
PubMed2006

A new challenge for malaria control in Brazil: asymptomatic Plasmodium infection--a review.

The evolution of malaria in Brazil, its morbidity, the malaria control programs, and the new challenges for these programs in the light of the emergence of asymptomatic infection in the Amazon region of Brazil were reviewed. At least six Brazilian research groups have demonstrated that asymptomatic infection by Plasmodium is an important impediment to malaria control, among mineral prospectors in Mato Grosso and riverside communities in Rondônia and, in our group, in the middle and upper reaches of the Negro river, in the state of Amazonas. Likewise, other researchers have studied the problem among indigenous communities in the Colombian, Peruvian, and Venezuelan parts of the Amazon basin, adjacent to Brazil. The frequency of positive results from the polymerase chain reaction (PCR) among asymptomatic individuals has ranged from 20.4 to 49.5%, and the presence of Plasmodium in the thick blood smears, from 4.2 to 38.5%. Infection with Anopheles darlingi has also been demonstrated by xenodiagnosis among asymptomatic patients with positive PCR results. If a mean of 25% is taken for the asymptomatic infection caused by Plasmodium sp. in the Amazon region of Brazil, malaria control will be difficult to achieve in that region with the measures currently utilized for such control.

Animals↗
PubMed1999

[Falciform anemia and Plasmodium falciparum malaria: a threat to flap survival?].

Plasmodium falciparum malaria, a parasitic disease, and sickle cell anemia, a hereditary disease, are two diseases affecting erythrocyte cycle, occurring with a high prevalence in tropical Africa. They may induce microthrombosis inducing vaso-occlusion, organ dysfunction and flap necrosis. During the acute phase of Plasmodium falciparum malaria, destruction of parasitized and healthy erythrocytes, release of parasite and erythrocyte material into the circulation, and secondary host reaction occur. Plasmodium falciparum infected erythrocytes also sequester in the microcirculation of vital organs and may interfere with microcirculatory flow in the flap during the postoperative period. The lower legs of homozygous sickle cell anemia patients are areas of marginal vascularity where minor abrasions become foci of inflammation. Inflammation results in decreased local oxygen tension, sickling of erythrocytes, increased blood viscosity and thrombosis with consequent ischemia, tissue breakdown and leg ulcer. Tissue transfer has become the procedure of choice for reconstruction of the lower third of the leg although flaps may become necrotic. The aim of this study is to analyse circumstances predisposing to surgical complications and to define preventive and therapeutic measures. A review of the literature will describe the current research and the new perspectives to treat sickle cell anemia, for example hydroxyurea and vasoactive substances (pentoxifylline, naftidrofuryl, buflomedil).

Anemia, Sickle Cell↗
PubMed2001

[Plasmodium vivax: therapy update].

IMPACT OF PLASMODIUM VIVAX WORLDWIDE: Plasmodium vivax is the most widespread malanal agent in the world. Unlike Plasmodium falciparum, P. vivax can cause early or late recurrence and is not fatal (benign tertian malaria). EMERGENCE OF RESISTANT STRAINS: P. vivax strains resistant to chloroquine, then primaquine, have emerged over the last decade, creating the need for a new therapeutic strategy. TREATMENT OF PRIMARY DISEASE: Generally, chloroquine is the first intention treatment, excepting patients who also have P. falciparum infection or a strain with suspected resistance to chloroquine. Mefloquine, quinine and halofantrine are also logical alternatives. TREATMENT OF RECURRENT DISEASE: A schizonticidal agent should be given followed by a hypnozoitocidal agent, primaquine. Primaquine dosage should now be raised or adjusted to the patient's weight. THERAPEUTIC PERSPECTIVES: Tafenoquine, delayed-release amino-8-quinoleine, is a potential alternative for primaquine for the treatment of recurrences. Studies are also in progress to evaluate the role of primaquine as a prophylaxic agent.

Animals↗
PubMed2000

[Epidemiological and therapeutic aspects of plasmodial infection from Plasmodium vivax].

A major challenge for successful treatment of Plasmodium vivax malaria is prevention of recurrence due to activation of dormant intrahepatic parasitic forms called hypnozoits. As a result of strain variability, recurrences are unpredictable and can occur months or even years after initial infection. Prevention requires elimination of both erythrocytic and hepatic parasite forms by combined use of chloroquine and primaquine. Primaquine is the only commercially available drug against hypnozoits. Several factors must be taken into account in planning treatment regimens. One factor is drug resistance of vivax strains, which as observed for Plasmodium falciparum strains is variable between geographical areas. Another factor is potential co-infection by Plasmodium vivax and falciparum, which is increasingly common. For optimal efficacy, treatment regimens must be adjusted with regard to dosage of primaquine and association with halofantrine, mefloquine or other new antimalarial agents. No regimen completely rules out the risk of recurrence.

Antimalarials↗
PubMedDate not supplied

Effect of Plasmodium falciparum parasitaemia on some haematological parameters in adolescent and adult Nigerian HbAA and HbAS blood genotypes.

OBJECTIVE: To compare the susceptibility of HbAA and HbAS blood genotypes to Plasmodium falciparum in human subjects. DESIGN: Prospective Cross Sectional Study. SETTINGS: Department of Biochemistry College of Medical Sciences, University of Calabar, Cross Rivers State, Nigeria. SUBJECTS: A total of 120 individuals comprising 60 subjects (41 males and 19 females) and 60 patients (33 males and 27 females) aged between 15 and 30 years were enlisted in this study. MAIN OUTCOME MEASURES: The susceptibility of the HbAA and HbAS blood genotypes to Plasmodium falciparum in human subjects was based on the frequency of occurrence of parasitaemia and the accompanying haematological changes in each group. RESULTS: Among a sample population of 120 subjects and patients, 86 were HbAA and 34 were HbAS representing 72% and 28% of the sample population. Parasites were detected in the red cells of 15 out of the 34 HbAS subjects i.e. 44% of the group or 13% of the sample population. Compared with the control group, the parasitaemic HbAA group had significantly lower PCV and Hb, and significantly higher serum iron, TIBC and transferrin, but a similar percentage transferrin saturation. All the differences were highly significant (p < 0.001). In the parasitaemic HbAS group, PCV and percentage transferrin saturation were slightly lower while TIBC and transferrin were slightly higher when compared with the control. These differences were not significant. CONCLUSION: The greater susceptibility of HbAA individuals to Plasmodium falciparum malaria and the enhanced severity of an attack in this group maybe due to low red cell membrane resistance to the invading parasite and a non-hypoxic environment within the red cell which enhances its development.

Adolescent↗
PubMed1995

[Plasmodium falciparum index and level of parasitemia: diagnostic and prognostic value in the Congo].

Parasitological data of various malarial studies performed in the Congo where Plasmodium falciparum malaria is holo-endemic in rural and suburban zones, between 1988 and 1991, were analyzed with the intention of establishing diagnosis and prognosis value of Plasmodium falciparum parasitaemia in areas with high perennial transmission. In such an area congolese school-children (6-10 years old) had 88% P. falciparum index, this is the same percentage as that for children hospitalized with a pernicious attack. However, the parasite load is distributed differently; parasitaemia is greater than 6,000 asexual form of P. falciparum/microliters (afPf/microL) in only 4.6% of cases in the former group versus 67% in the second group. A threshold of 10,000 afPf/microliters, above which the Plasmodium infection triggers a febrile attack in semi-immune children, is confirmed in school children in a rural context where the factor of taking antimalarial drugs within the preceding days is negligible; three out of four children with levels above this threshold are febrile versus 4.1% (7 out of 170) with lower blood parasite levels. Some adults were also asymptomatic carriers but much less frequently and with lower mean parasitaemia levels. The parasite load mirrors the clinical severity although this concept can be misleading as an individual prognostic criterion and for hospital studies carried out in areas where multiple drug administration before hospitalisation is common. For the studies recently performed in Brazzaville, the 5% threshold level of parasitized red cells, the WHO severity criterion, was never reached in asymptomatic subject or in cases of simple attack; it was reached in one out of two cases of pernicious attack.

Adolescent↗
PubMed1995

[Role of modulators in Plasmodium falciparum resistance to antimalarials].

Modulating agents that circumvent the Plasmodium falciparum resistance to antimalarials are components without any intrinsic antimalarial activity but able, in association with a standard antimalarial drug, to restore the sensitivity of Plasmodium falciparum to this drug. Two hypotheses are forwarded about their possible mechanisms of action : the mechanisms involving the inhibition of the drug efflux and the mechanisms involving the inhibition of antimalarial drug metabolic degradation. None of these mechanisms is able to alone explain the effect of all modulating agents. The future use prospects of these compounds are limited by their in vivo toxicity. That relevant to the calcium channels blockers seems to be circumvented by the use of dextro-enantiomers. A toxicity relevant to a possible accumulation of the antimalarial in healthy, non target cells must be also suspected. Moreover the use of these agents evidences a socio-economic problem : a complete new development of the association (antimalaria plus modulatin drugs) is needed and that, in developing countries. Nevertheless, the agents modulating the Plasmodium falciparum resistance are a new approach for the treatment of resistant malaria which might give a recrudescence of activity to the old antimalarials as chloroquine.

Animals↗
PubMed1993

Morphological changes of clefts in Plasmodium-infected erythrocytes under adverse conditions.

Blood infected with human or rodent malaria parasites, Plasmodium falciparum or Plasmodium berghei, was exposed to higher pH, higher PO2, and lower temperature than those used in standard cultivation conditions. Parasitized blood was incubated for 20, 25, and 30 min with RPMI 1640 medium, 10% (vol/vol) serum, pH 8.0, at 20 degrees C in the air, conditions which are ultimately lethal to the asexual stages of malarial parasites. Markedly dilated clefts were observed in the cytoplasm of the malaria-infected erythrocytes so treated. These clefts can take up colloidal gold particles and macromolecules such as Protein A, rhodamine-dextran, and lucifer yellow-dextran. Such dilated clefts were not seen in the cytoplasm of infected erythrocytes that were incubated under normal cultivation conditions before fixation. These had slender clefts of the usual sort that did not take up colloidal gold particles and macromolecules.

Animals↗
PubMed2004

The efficacy of inhibitors involved in spermidine metabolism in Plasmodium falciparum, Anopheles stephensi and Trypanosoma evansi.

In the present study, we have tested the effect of different polyamine inhibitors of the spermidine metabolizing enzymes deoxyhypusine synthase and homospermidine synthase in different chloroquine resistant Plasmodium falciparum strains, in the mosquito Anopheles stephensi (Diptera: Culicidae) and in a Trypanosoma evansi clone I from strain STIB 806 K China. Recent experiments have shown that agmatine is a growth inhibitor of the malaria parasite P. falciparum (Kaiser et al. 2001) in vitro. A comparison of agmatine efficacy with the new antimalarials artemisinin, triclosan and conventional chloroquine showed similar or even better results on the basis of growth inhibition and the reduction of developmental forms. However, no effect of triclosan or agmatine was observed at the ribonucleic acid level. In a second set of experiments, we tested the effect of 1,7-diaminoheptane and agmatine on oocyst formation in A. stephensi after infection with Plasmodium yoelii. Agmatine had an antisporozoite effect since 1,000 microM led to a 59.5% inhibition of oocysts. A much weaker inhibitor of oocyst formation was 1,7-diaminoheptane. The most effective in in vitro inhibition of T. evansi was dicyclohexylamine, an inhibitor of spermidine biosynthesis with an IC(50 ) value of 47.44 microM and the deoxyhypusine inhibitor 1,7-diaminoheptane with an IC(50) value of 47.80 microM. However, both drugs were ineffective in in vivo experiments in a Trypanosoma mouse model. Two different spermidine analogues, 1,8-diaminooctane and 1,3-diaminopropane with IC(50) values of 171 microM and 181.37 microM, respectively, were moderate inhibitors in vitro and ineffective in vivo.

Animals↗
PubMed2006

Standardization of a very specific and sensitive single PCR for detection of Plasmodium vivax in low parasitized individuals and its usefulness for screening blood donors.

Here, we describe the standardization of a very sensitive and specific single Plasmodium vivax polymerase chain reaction (PCR) and its usefulness for diagnosis and screening procedures when a Plasmodium falciparum PCR was also utilized. The P. vivax PCR sensitivity threshold was 0.019 parasites per microliter, and a PCR fragment was only detected when P. vivax DNA was present. Among the 11 febrile patients with negative parasitological examination that attended the malaria service of Fundação de Medicina Tropical do Amazonas, we diagnosed one P. vivax malaria by PCR. Among the 286 individuals considered suitable for blood donation, we also detected by PCR an individual with P. vivax malaria, and conversely, we did not detect any malaria infection in blood donor candidates considered unsuitable due to its past malaria history. We conclude that PCR is the method of choice for low-parasitized individuals and could therefore represent a complementary tool to safely rescue blood donor candidates considered unsuitable on the basis of malaria history.

Animals↗
PubMed1988

Plasmodium falciparum: purification, properties, and immunochemical study of ornithine decarboxylase, the key enzyme in polyamine biosynthesis.

Ornithine decarboxylase, the rate-limiting enzyme in the polyamine biosynthetic pathway has been purified 7,600 fold from Plasmodium falciparum by affinity chromatography on a pyridoxamine phosphate column. The partially purified enzyme was specifically tagged with radioactive DL-alpha-difluoromethylornithine and subjected to polyacrylamide gel electrophoresis under denaturing conditions. A major protein band of 49 kilodalton was obtained while with the purified mouse enzyme, a typical 53 kilodalton band, was observed. The catalytic activity of parasite enzyme was dependent on pyridoxal 5'-phosphate and was optimal at pH 8.0. The apparent Michaelis constant for L-ornithine was 52 microM. DL-alpha-difluoromethylornithine efficiently and irreversibly inhibited ornithine decarboxylase activity from P. falciparum grown in vitro or Plasmodium berghei grown in vivo. The Ki of the human malarial enzyme for this inhibitor was 16 microM. Ornithine decarboxylase activity in P. falciparum cultures was rapidly lost upon exposure to the direct product, putrescine. Despite the profound inhibition of protein synthesis with cycloheximide in vitro, parasite enzyme activity was only slightly reduced by 75 min of treatment, suggesting a relatively long half-life for the malarial enzyme. Ornithine decarboxylase activity from P. falciparum and P. berghei was not eliminated by antiserum prepared against purified mouse enzyme. Furthermore, RNA or DNA extracted from P. falciparum failed to hybridize to a mouse ornithine decarboxylase cDNA probe. These results suggest that ODC from P. falciparum bears some structural differences as compared to the mammalian enzyme.

Animals↗